A muscular dystrophy is a group of diseases that cause progressive weakness and loss of muscle mass. In muscular dystrophy, abnormal genes (mutations) interfere with the production of proteins needed to form healthy muscle.
There are many different kinds of muscular dystrophy. Symptoms of the most common variety begin in childhood, mostly in boys. Other types don’t surface until adulthood.
The main sign of muscular dystrophy is progressive muscle weakness. Specific signs and symptoms begin at different ages and in different muscle groups, depending on the type of muscular dystrophy.
Becker muscular dystrophy
Signs and symptoms are similar to those of Duchenne muscular dystrophy but tend to be milder and progress more slowly. Symptoms generally begin in the teens but may not occur until the mid-20s or even later.
Duchenne muscular dystrophy (DMD)
This is the most common form of muscular dystrophy.
It is caused by an absence of dystrophin, a protein that helps keep muscle cells intact. Lack of dystrophin protein in muscle cells causes them to be fragile and easily damaged.
DMD has an X-linked recessive inheritance pattern and is passed on by the mother, who is referred to as a carrier. About one-third of boys with Duchenne muscular dystrophy (DMD) don’t have a family history of the disease, possibly because the gene involved may be subject to sudden abnormal change (spontaneous mutation).
Symptom onset is in early childhood, usually between ages 3 and 5. The disease primarily affects boys, but in rare cases, it can affect girls.
Signs and symptoms typically appear in early childhood include:
Proximal weakness causes a waddling gait and difficulty climbing stairs, running, jumping, and standing up from a squatting position. DMD is rapidly progressive, with affected children being wheelchair dependent by age 12 years. Cardiomyopathy occurs in almost all individuals with DMD after age 18 years. Few survive beyond the third decade, with respiratory complications and progressive cardiomyopathy being common causes of death. Becker muscular dystrophy (BMD) is characterized by later-onset skeletal muscle weakness.
- Frequent falls
- Difficulty rising from a lying or sitting up position
- Trouble running and jumping
- Waddling gait
- Walking on the toes
- Large calf muscles
- Muscle pain and stiffness
- Learning disabilities
Mutations in the DMD gene cause the Duchenne and Becker forms of muscular dystrophy. The DMD gene provides instructions for making a protein called dystrophin. This protein is located primarily in skeletal and cardiac muscle, where it helps to stabilize and protect muscle fibers. Dystrophin may also play a role in chemical signaling within cells.
Mutations in the DMD gene alter the structure or function of dystrophin or prevent any functional dystrophin from being produced. Muscle cells without enough of this protein become damaged as muscles repeatedly contract and relax with use. The damaged fibers weaken and die over time, leading to the muscle weakness and heart problems characteristic of Duchenne and Becker muscular dystrophies. Mutations that lead to an abnormal version of dystrophin that retains some function usually cause Becker muscular dystrophy, while mutations that prevent the production of any functional dystrophin tend to cause Duchenne muscular dystrophy.
Because Duchenne and Becker muscular dystrophies result from faulty or missing dystrophin, these conditions are classified as dystrophinopathies.
TESTS USED TO DIAGNOSE DMD/BMD
In diagnosing any form of muscular dystrophy, a doctor usually begins by taking a patient and family history and performing a physical examination. Much can be learned from these, including the pattern of weakness. The history and physical go a long way toward making the diagnosis, even before any complicated diagnostic tests are done.
Early in the diagnostic process, doctors often order a blood test called a CK level. CK stands for creatine kinase, an enzyme that leaks out of the damaged muscle. When elevated CK levels are found in a blood sample, it usually means the muscle is being destroyed by some abnormal process, such as muscular dystrophy or inflammation. A very high CK level suggests that the muscles themselves (and not the nerves that control them) are the likely cause of the weakness, although it doesn’t tell exactly what the muscle disorder might be.
To obtain more information, the doctor may order a muscle biopsy, the surgical removal of a small sample of muscle from the patient. By examining this sample, doctors can tell a great deal about what’s actually happening inside the muscles.
Modern techniques can use the biopsy to distinguish muscular dystrophies from inflammatory and other disorders, and also to distinguish among different forms of muscular dystrophy. For instance, the amount of functional dystrophin protein found in a muscle biopsy sample sheds light on whether the disease course is likely to be DMD (with no dystrophin present) or the milder Becker muscular dystrophy (with some partially functional dystrophin present).
Genetic testing involves analyzing the DNA of any cells (usually blood cells are used) to see whether there is a mutation in the dystrophin gene.
Female relatives of men and boys with DMD can undergo DNA testing to see if they are carriers of the disease. Women who are DMD carriers can pass on the disease to their sons and their carrier status to their daughters. In a minority of cases, girls and women who are DMD carriers may themselves show symptoms of DMD, such as muscle weakness and heart problems. These symptoms may not show up until adulthood.
The genetic diagnosis is not easily made because of the large size of the dystrophin gene, complex mutational spectrum and a high number of tests patients undergo for diagnosis. Multiplex ligation-dependent probe amplification (MLPA) has been used as the initial diagnostic test of choice. Although MLPA can diagnose 70% of DMD/BMD patients having deletions/duplications, the remaining 30% of patients with small mutations require further analysis, such as Sanger sequencing.
Additional Resources for Duchenne Muscular Dystrophy